Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice

doi:10.1038/s41401-022-00915-5

	Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice
	Chen, Ye-ru 1; Zhang, Shu-xia 1; Fang, Man 1,3; Zhang, Piao 1; Zhou, You-fa 1; Yu, Xin 1; Zhang, Xiang-nan 2; Chen, Gang 1
刊名	ACTA PHARMACOLOGICA SINICA
	2022-05-16
关键词	sevoflurane learning ability impairment hippocampus early growth response 2 brain-derived neurotrophic factor dendritic spins nuclear factors of activated T-cell
ISSN号	1671-4083
DOI	10.1038/s41401-022-00915-5
通讯作者	Chen, Gang(chengang120@zju.edu.cn)
英文摘要	Sevoflurane inhalation is prone to initiate cognitive deficits in infants. The early growth response-2 (Egr-2) gene is DNA-binding transcription factor, involving in cognitive function. In this study we explored the molecular mechanisms underlying the vulnerability to cognitive deficits after sevoflurane administration. Six-day-old (young) and 6-week-old (early adult) mice received anesthesia with 3% sevoflurane for 2 h daily for 3 days. We showed that multiple exposures of sevoflurane induced significant learning ability impairment in young but not early adult mice, assessed in Morris water maze test on postnatal days 65. The integrated differential expression analysis revealed distinct transcription responses of Egr family members in the hippocampus of the young and early adult mice after sevoflurane administration. Particularly, Egr2 was significantly upregulated after sevoflurane exposure only in young mice. Microinjection of Egr2 shRNA recombinant adeno-associated virus into the dentate gyrus alleviated sevoflurane-induced cognitive deficits, and abolished sevoflurane-induced dendritic spins loss and BDNF downregulation in young mice. On the contrary, microinjection of the Egr2 overexpression virus in the dentate gyrus aggravated learning ability impairment induced by sevoflurane in young mice but not early adult mice. Furthermore, we revealed that sevoflurane markedly upregulated the nuclear factors of activated T-cells NFATC1 and NFATC2 in young mice, which were involved in Egr2 regulation. In conclusion, Egr2 serves as a critical factor for age-dependent vulnerability to sevoflurane-induced cognitive deficits.
资助项目	National Natural Science Foundation of China[82171176] ; National Natural Science Foundation of China[82001424] ; Zhejiang Provincial Natural Science Foundation of China[LQ19H030009] ; Key Program of the Natural Science Foundation of Zhejiang, China[LZ19H090003]
WOS关键词	TRANSCRIPTION FACTOR ; BEHAVIORAL OUTCOMES ; DENDRITIC SPINES ; GENE-EXPRESSION ; EARLY EXPOSURE ; BRAIN ; ANESTHESIA ; IMPAIRMENT ; INDUCTION ; NEUROTOXICITY
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBL GROUP
WOS记录号	WOS:000796322300001
资助机构	National Natural Science Foundation of China ; Zhejiang Provincial Natural Science Foundation of China ; Key Program of the Natural Science Foundation of Zhejiang, China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/130953]
专题	中国科学院合肥物质科学研究院
通讯作者	Chen, Gang
作者单位	1.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Anesthesiol, Hangzhou 310058, Peoples R China 2.Zhejiang Univ, Minist Hlth China, Key Lab Med Neurobiol, Coll Pharmaceut Sci,Inst Pharmacol & Toxicol, Hangzhou 310058, Peoples R China 3.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Zhejiang Canc Hosp, Univ Chinese Acad Sci,Canc Hosp, Hangzhou 310022, Peoples R China
推荐引用方式 GB/T 7714	Chen, Ye-ru,Zhang, Shu-xia,Fang, Man,et al. Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice[J]. ACTA PHARMACOLOGICA SINICA,2022.
APA	Chen, Ye-ru.,Zhang, Shu-xia.,Fang, Man.,Zhang, Piao.,Zhou, You-fa.,...&Chen, Gang.(2022).Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice.ACTA PHARMACOLOGICA SINICA.
MLA	Chen, Ye-ru,et al."Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice".ACTA PHARMACOLOGICA SINICA (2022).